Radiographic assessment of ground-level falls in elderly patients: Is the "PAN-SCAN" overdoing it?

INTRODUCTION: Routine, whole-body computed tomography imaging (PAN-SCAN) has been shown to identify unexpected injuries and alter the management of patients presenting with blunt trauma. We sought to characterize the changes in practice over time and the utility of PAN-SCAN imaging in elderly patients who fall and require admission to a trauma center. METHODS: We performed a retrospective analysis by using data derived from a Pennsylvania state-wide trauma registry (2007-2010). All hemodynamically stable patients (>65 years) who had a ground-level fall and were admitted for >24 hours were selected. Patients who underwent a combination of all three scans within 2 hours of arrival were considered to have underwent PAN-SCAN imaging. Clinical outcomes were compared across PAN-SCAN patients relative to less diagnostic imaging. Regression analysis was used to determine whether PAN-SCAN imaging was an independent determinate of mortality and resource use. RESULTS: Over the period of study, 13,043 patients met inclusion criteria. The annual rate of PAN-SCAN imaging after ground-level falls increased over time. After we controlled for important confounders, PAN-SCAN imaging was not associated with mortality (odds ratio 0.97, P = .74, 95% confidence interval 0.80-1.18). Despite greater injury severity, PAN-SCAN imaging was independently associated with significantly lesser intensive care unit requirements, step-down days, and a lesser overall duration of stay. CONCLUSION: PAN-SCAN imaging has become more common over time in elderly patients having a ground-level fall. Although PAN-SCAN imaging during the initial trauma evaluation was not associated with an independent decrease in the risk of mortality, it was independently associated with lesser hospital resource use. These data suggest that whole-body computed tomography imaging may benefit trauma center resource use for patients with ground-level falls.

Why human cytochrome P450c21 is a progesterone 21-hydroxylase.

Human cytochrome P450c21 (steroid 21-hydroxylase, CYP21A2) catalyzes the 21-hydroxylation of progesterone (P4) and its preferred substrate 17α-hydroxyprogestrone (17OHP4). CYP21A2 activities, which are required for cortisol and aldosterone biosynthesis, involve the formation of energetically disfavored primary carbon radicals. Therefore, we hypothesized that the binding of P4 and 17OHP4 to CYP21A2 restricts access of the reactive heme-oxygen complex to the C-21 hydrogen atoms, suppressing oxygenation at kinetically more favorable sites such as C-17 and C-16, which are both hydroxylated by cytochrome P450c17 (CYP17A1). We reasoned that expansion of the CYP21A2 substrate-binding pocket would increase substrate mobility and might yield additional hydroxylation activities. We built a computer model of CYP21A2 based principally on the crystal structure of CYP2C5, which also 21-hydroxylates P4. Molecular dynamics simulations indicate that binding of the steroid nucleus perpendicular to the plane of the CYP21A2 heme ring limits access of the heme oxygen to the C-21 hydrogen atoms. Residues L107, L109, V470, I471, and V359 were found to contribute to the CYP21A2 substate-binding pocket. Mutation of V470 and I471 to alanine or glycine preserved P4 21-hydroxylase activity, and mutations of L107 or L109 were inactive. Mutations V359A and V359G, in contrast, acquired 16α-hydroxylase activity, accounting for 40% and 90% of the P4 metabolites, respectively. We conclude that P4 binds to CYP21A2 in a fundamentally different orientation than to CYP17A1 and that expansion of the CYP21A2 substrate-binding pocket allows additional substrate trajectories and metabolic switching.